In December 2015, Alcensa received accelerated approval for treatment of patients with ALK-positive metastatic NSCLC whose disease progressed on or who were intolerant of Xalkori (crizotinib) based on an independent review committee (IRC)-assessed overall response rate (ORR) of 38% and 44% among 87 and 138 patients, respectively, in two single arm trials.

This current approval is based on data from ALEX (NCT02075840), a randomized, multi-center, open-label, active-controlled trial conducted in 303 patients with ALK-positive NSCLC who had not received prior systemic therapy for metastatic disease. All patients were required to have evidence of ALK-rearrangement identified by the VENTANA ALK (D5F3) CDx Assay performed through central laboratory testing. Patients were randomized 1:1 to receive Alcensa 600 mg orally twice daily (n=152) or 250 mg orally twice daily (n=151).

ALEX demonstrated an improvement in progression-free survival (PFS) as assessed by blinded IRC (BIRC), with a hazard ratio (HR) of 0.53 (95% CI: 0.38, 0.73; p<0.0001). The estimated median PFS for patients randomized to Alcensa was 25.7 months (95% CI: 19.9, not estimable [NE]) compared with 10.4 months (95% CI: 7.7, 14.6) for those randomized to Xalkori. The time to cause-specific central nervous system (CNS) progression as assessed by IRC was also significantly improved; there was a lower incidence of progression in the CNS as first site of disease progression, alone or concurrent with systemic progression, in the Alcensa arm (12%) compared to the Xalkori arm (45%). Confirmed ORR was 79% (95% CI: 72, 85) and 72% (95% CI: 64, 79) in the Alcensa and Xalkori arms, respectively. Among the 120 responders in the Alcensa arm and the 109 responders in the Xalkori arm, the proportion of patients with response duration of ≥12 months was 64% and 36%, respectively.

CNS involvement was assessed in all patients. Among the 43 patients with measurable CNS lesions on baseline brain scans, the CNS ORR, assessed by BIRC neuro-radiologist, was 81% (95% CI: 58, 95) in the Alcensa arm and 50% (95% CI: 28, 72) in the Xalkori arm. Among patients with measurable CNS lesions and a CNS response, the proportion of patients with a CNS response duration of ≥12 months was 59% in the Alcensa arm and 36% in the Xalkori arm.